Identification of Novel Genetic Markers of Breast Cancer Survival

被引：49

作者：

Guo, Qi ^{[1
]}

Schmidt, Marjanka K. ^{[2
]}

Kraft, Peter ^{[3
,4
]}

Canisius, Sander ^{[2
]}

Chen, Constance ^{[4
]}

Khan, Sofia ^{[6
]}

Tyrer, Jonathan ^{[1
]}

Bolla, Manjeet K. ^{[6
]}

Wang, Qin ^{[6
]}

Dennis, Joe ^{[6
]}

Michailidou, Kyriaki ^{[6
]}

Lush, Michael ^{[6
]}

Kar, Siddhartha ^{[5
]}

Beesley, Jonathan ^{[7
]}

Dunning, Alison M. ^{[1
]}

Shah, Mitul ^{[1
]}

Czene, Kamila ^{[8
]}

Darabi, Hatef ^{[8
]}

Eriksson, Mikael ^{[8
]}

Lambrechts, Diether ^{[9
,10
]}

Weltens, Caroline ^{[11
]}

Leunen, Karin ^{[11
]}

Bojesen, Stig E. ^{[12
,13
,14
]}

Nordestgaard, Borge G. ^{[12
,13
,14
]}

Nielsen, Sune F. ^{[12
,13
]}

Flyger, Henrik ^{[15
]}

Chang-Claude, Jenny ^{[16
]}

Rudolph, Anja ^{[16
]}

Seibold, Petra ^{[16
]}

Flesch-Janys, Dieter ^{[17
,18
]}

Blomqvist, Carl ^{[19
]}

Aittomaeki, Kristiina ^{[20
]}

Fagerholm, Rainer ^{[5
]}

Muranen, Taru A. ^{[5
]}

Couch, Fergus J. ^{[21
,101
]}

Olson, Janet E. ^{[22
]}

Vachon, Celine ^{[22
]}

Andrulis, Irene L. ^{[23
,24
]}

Knight, Julia A. ^{[25
,26
]}

Glendon, Gord ^{[24
]}

Mulligan, Anna Marie ^{[27
,28
]}

Broeks, Annegien ^{[2
]}

Hogervorst, Frans B. ^{[2
]}

Haiman, Christopher A. ^{[29
]}

Henderson, Brian E. ^{[29
]}

Schumacher, Fredrick ^{[29
]}

Le Marchand, Loic ^{[30
]}

Hopper, John L. ^{[31
,49
]}

Tsimiklis, Helen ^{[32
]}

Apicella, Carmel ^{[31
]}

机构：

[1] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England

[2] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands

[3] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA

[5] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland

[6] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England

[7] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia

[8] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden

[9] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium

[10] VIB, Vesalius Res Ctr, Leuven, Belgium

[11] Univ Hosp Gasthuisberg, Dept Oncol, Leuven, Belgium

[12] Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark

[13] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark

[14] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark

[15] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark

[16] German Canc Res Ctr, Div Canc Epidemiol, Deutsch Krebsforschungszentrum, Heidelberg, Germany

[17] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany

[18] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany

[19] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland

[20] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland

[21] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[22] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[23] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[24] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada

[25] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada

[26] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada

[27] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[28] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada

[29] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[30] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA

[31] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

[32] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia

[33] Univ Sheffield, Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England

[34] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England

[35] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[36] Alfred Hosp, Anat Pathol, Melbourne, Vic, Australia

[37] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland

[38] Univ Oulu, Bioctr Oulu, Oulu, Finland

[39] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland

[40] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland

[41] Univ Oulu, Dept Surg, Oulu Univ Hosp, Oulu, Finland

[42] Erasmus MC Canc Inst, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands

[43] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[44] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany

[45] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany

[46] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[47] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[48] Frederick Natl Lab Canc Res, Core Genotyping Facil, Gaithersburg, MD USA

[49] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland

[50] Kings Coll London, Guys & St Thomas NHS Fdn Trust, Comprehens Biomed Res Ctr, Div Canc Studies,NIHR, London WC2R 2LS, England

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2015年 / 107卷 / 05期

基金：

英国医学研究理事会; 美国国家卫生研究院; 加拿大健康研究院; 芬兰科学院;

关键词：

GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; PROGNOSIS; RISK; CYCLOPHOSPHAMIDE; EPIRUBICIN; DIAGNOSIS; CYP19A1; TUMOR; LOCI;

D O I：

10.1093/jnci/djv081

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. Methods: We conducted a large meta-analysis of studies in populations of European ancestry, including 37 954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200 000 and 900 000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23 059 ER-positive patients (1333 events). All statistical tests were two-sided. Results: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. Conclusions: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.

引用

页数：9

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